ObjectiveTo explore the molecular characteristics of partial epilepsy with febrile seizures plus(PEFS+). MethodsWe systematically reviewed all SCN1A mutation-related publications that published between Jan.2000 and Dec.2014 on Pubmed and established a database of SCN1A mutations (http://www.gzneurosci.com/SCN1Adatabase/). The characteristics of mutations that cause PEFS+ were analyzed and compared with that of severe myoclonic epilepsy in infancy (SMEI). ResultsThe database included 1, 257 SCN1A mutations, which identified from 1, 727 unrelated cases. In which there were 30 mutations, from 32 unrelated cases, were associated with PEFS+. 76.7% (23/30) mutations were missense, of which 47.8% (11/23) were located on pore region. Significant difference in the percentage of truncation mutation was observed between PEFS+ and SMEI (P < 0.05). There was no significant difference in the percentage of missense mutation that located on the pore region between PEFS+ and SMEI; but the differ significantly in D-value of the missense mutations, which quantified the alteration of amino acid(P=0.042, rank sum test). ConclusionsPEFS+, which distinguishes from GEFS+ and SMEI in clinical and molecular characteristics, is a special phenotype of epilepsy that is associated with SCN1A mutations.
ObjectivesTo evaluate the efficacy and safety of lacosamide (200mg/d and 400mg/d)when added to 1 to 3 antiepileptic drugs (AEDs) in adults with uncontrolled partial-onset seizures. MethodsDuring this multicenter, double-blind, placebo-controlled trial, patients were randomized to placebo or lacosamide 200 or 400mg/day after an 8-week baseline period. Lacosamide was titrated in weekly increments to target dose over 4 weeks and maintained for 12 weeks followed by 12 weeks for withdrawal. The reductions of seizure frequence during maintain period and proportion of ≥50% reduction of seizures frequence were analysed. Besides,adverse effects were also recorded. ResultsFive hundred fourty patients were randomized, 515 patients completed the trial (Full analysis set, FAS), including 394 were per-protocol set (PPS). The reduction of seizure frequence during maintain period every 4 weeks among 200mg/d,400mg/d group and placebo group were 26.35%,40.12%,21.69%(P=0.000 5) and 25.61%,46.86%,23.06%(P<0.000 1), respectively in FAS and PPS. The proportion of ≥50% reduction of seizures frequence among three groups were 29.82%,38.15%,22.49%(P=0.006 8) and 27.94%,42.37%,22.86%(P=0.002 3), respectively in FAS and PPS. The incidences of adverse events were 5.84%, 36.11%, 19.55% among three groups. Compared with each other, there was statistic significance between 400mg/d and placebo groups. ConclusionIn this trial, adjunctive lacosamide significantly reduced seizure frequency in patients with uncontrolled partial-onset seizures. Along with favorable pharmacokinetic and tolerability profiles, these results support further development of lacosamide as an AED.